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雄激素受体(androgen receptor,AR)是核受体超家族中的成员,主要以雄激素依赖的方式诱导下游靶基因转录。在此过程中,AR招募辅调节因子参与调控下游靶基因转录,从而发挥其生物学功能。近年研究证实,AR在肝细胞肝癌(hepatocellular carcinoma,HCC)发生发展中发挥重要作用。一方面,AR介导的下游靶基因(TGF-β1、VEGF、CCRK等)的异常表达影响HCC细胞的生长、增殖、血管形成等进程。乙肝病毒HBV X蛋白通过激活c-Src激酶等途径上调AR的转录活性,从而促进HCC的发展。另一方面,还有研究证实,AR可抑制HCC细胞的转移。现主要综述AR介导的基因转录调控在HCC中作用的分子机制,这将为HCC的早期发现及治疗提供理论依据和新的思路。
Androgen receptor (AR), a member of the nuclear receptor superfamily, induces downstream target gene transcription mainly in an androgen-dependent manner. In this process, AR recruitment regulators mediate transcription of downstream target genes to exert their biological functions. Recent studies have confirmed that AR plays an important role in the development of hepatocellular carcinoma (HCC). On the one hand, the abnormal expression of AR-mediated downstream target genes (TGF-β1, VEGF, CCRK, etc.) affects the process of HCC cell growth, proliferation and angiogenesis. Hepatitis B virus HBV X protein enhances the transcriptional activity of AR by activating c-Src kinase and other pathways, thereby promoting the development of HCC. On the other hand, studies have confirmed that AR can inhibit the metastasis of HCC cells. This review summarizes the molecular mechanism of AR-mediated gene transcriptional regulation in HCC, which will provide theoretical basis and new ideas for the early detection and treatment of HCC.